Alpha 2-Macroglobulin is a primary human plasma protease inhibitor. Although alpha 2M is partially responsible for the regulation of many physiological processes and for the rapid clearance of activated protease, little is known about the molecular bases of its inhibition. Using peptide sequencing methodology the site of protease interaction with alpha 2M will be determined. The specific site of methylamine inhibition of alpha 2M will be studied. The structure of protein-bound chromophore will be determined. The conformational changes in alpha 2M upon binding protease will be studied by measuring changes in alpha 2M carbohydrate and changes in the polarized fluorescence of covalent chromophores. Organization of the subunits in the native alpha 2M molecule will be studied by sequencing of disulfide peptides.